Pharmacological management of neurocognitive impairment in schizophrenia: A narrative review.

BACKGROUND: Cognitive impairment are among the core features of schizophrenia, experienced by up to 75% of patients. Available treatment options for schizophrenia including dopamine antagonists and traditional antipsychotic medications have not been shown to confer significant benefits on cognitive deficits. Contrary to the focus on management of positive symptoms in schizophrenia, cognitive abilities are main predictor of independent living skills, functional abilities, employment, engagement in relapse prevention, and patients' subjective sense of well-being and quality of life. This review aims to provide a summary of recent literature on pharmacological options for the treatment of cognitive deficits in schizophrenia. METHODS: We conducted a literature search of studies from 2011 to 2021 across four electronic databases including PubMed, PsycInfo, MEDLINE, and Embase. Human studies using a pharmacological treatment for cognitive impairment in schizophrenia were included. RESULTS: Fifty-eight eligible publications, representing 11 pharmacological classes, were included in this review. Major limitations involved small sample size, methodological limitations as well as heterogeneity of participants and outcome measures. CONCLUSIONS: Overall evidence remains inconclusive for any pharmacological classes studied for the treatment of cognitive deficits in schizophrenia. Methodological limitations in a majority of the studies rendered their findings preliminary. We further discuss possible explanations for these findings that could guide future research.

Comparison of Extrapyramidal Symptoms Among Outpatients With Schizophrenia on Long-Acting Injectable Antipsychotics.

BACKGROUND: Extrapyramidal symptoms (EPSs) are adverse effects of antipsychotics. Different risks of EPSs have been attributed to the 3 classes of antipsychotics. This study aimed to assess EPS in a clinical sample of schizophrenia patients who are on LAI and compare the severity of EPSs among the following 3 antipsychotic groups: (1) partial agonist, (2) second-generation antipsychotics, and (3) first-generation antipsychotics. METHODS: Ninety-two patients were recruited from the Schizophrenia Program Injection Clinic. Using the Extrapyramidal Symptom Rating Scale (ESRS), severity of EPS was assessed and information regarding factors associated with risk of EPS, including coprescriptions, comorbidities, and demographics, was obtained from medical charts. Group differences in ESRS scores and subscores were analyzed using 1-way analyses of variances. RESULTS: Among the 3 groups, there was no significant difference in total ESRS scores and subscores. Risperidone was associated with higher ESRS scores when compared with paliperidone, aripiprazole, and flupenthixol. Doses above maximum were commonly used in the paliperidone group, and there was no significant difference in total ESRS scores between the low, average, or above-maximum doses of paliperidone. CONCLUSIONS: Our results demonstrated a comparative risk of EPS across all 3 antipsychotic classes. Risperidone was associated with more EPS compared with other medications. A higher threshold for the "maximum dose" of paliperidone could be considered and higher doses used with the same cautions as low-average doses.

Limitations of access to antipsychotics in Canada: loss of the old and unavailability of the new options.

Schizophrenia is a severe, debilitating disorder that is associated with a significant burden of illness. Antipsychotic medications remain the mainstay of treatment for schizophrenia and related disorders. In recent years, a number of new psychotropic medications have been introduced to the market, with some potential differences in the mechanism of action compared to the previous ones. In this paper, we discuss the issue of lack of access to the newer antipsychotics in Canada, and the discontinuation of some of the older options from the market, leaving clinicians and patients with a limited number of available options. While the aim of this paper is to increase awareness of the current state of availability and accessibility of options, we further discuss some potential solutions.

Complete blood count inflammatory markers in treatment-resistant schizophrenia: Evidence of association between treatment responsiveness and levels of inflammation.

Accumulating evidence suggests that the variable response to antipsychotic treatment in schizophrenia reflects distinct biological subtypes. The pathophysiology of schizophrenia is associated with alteration in the immune system which can be measured with complete blood count (CBC) markers of systemic inflammation, including the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR). While previous research suggested a decrease in CBC inflammatory markers following treatment, it is unknown if treatment or response to treatment is associated with CBC markers in treatment-resistant schizophrenia. Here, we retrospectively analyzed the CBC at admission and discharge in schizophrenia inpatients classified as treatment-responsive, treatment-resistant, and ultra-treatment-resistant. Despite similar NLR at admission, the subtypes manifested different changes in NLR during treatment resulting in significant differences at discharge. Only the treatment-responsive group presented a significant decrease in inflammatory markers after treatment. Additionally, we found that the responsive group had a higher PLR at admission and was the only subgroup to demonstrate a significant reduction following treatment. In sum, our results support the idea that persistent inflammation is a biological trait marker of treatment resistance in schizophrenia.

Retrospective review of use of adjunctive psychostimulants in patients with schizophrenia.

BACKGROUND: Adjunctive psychostimulants have been proposed as a potential treatment option for the management of cognitive and/or negative symptoms of schizophrenia. METHODS: The present study is a retrospective review of use of adjunctive psychostimulants among outpatients enrolled in our tertiary Schizophrenia Program between 2014 and 2019. We assessed response to treatment, adverse effects, and the impact of various clinical factors on treatment outcome. RESULTS: Of the 77 (out of 1,300) participants prescribed psychostimulants during the study period, 42.22% had chart-based evidence of significant improvement, 27.77% had minimal improvement, and 25.55% reported no change. The majority (61.9%) demonstrated improvement in attention, concentration, and/or other cognitive symptoms. Approximately one-third of cases had evidence of emergence of psychosis. Of the factors assessed, comorbid attention-deficit/hyperactivity disorder was associated with an increased likelihood of response, and higher doses of stimulants were associated with likelihood of emergence of psychosis. CONCLUSIONS: Adjunctive psychostimulants could be a potential treatment consideration to address cognitive deficits in selected patients with schizophrenia.

Implications of the COVID-19 pandemic for patients with schizophrenia spectrum disorders: narrative review.

BACKGROUND: COVID-19 was declared a pandemic in March 2020, by the World Health Organization. The pandemic has had unprecedented worldwide implications, in particular on marginalized populations. AIMS: The aim of this study is to review the impact of the pandemic on patients with schizophrenia spectrum disorders. METHOD: A number of databases were searched for this review, including PubMed, EMBASE, PsycINFO and Google Scholar. Search terms included psychosis and COVID-19, schizophrenia and COVID-19, and severe mental illness and COVID-19. We included all English language papers and preprints. The final search was done on 15 July 2020. RESULTS: Forty-seven relevant studies were identified and included in this review. Studies were summarised into five main subcategories: potential impact of the COVID-19 pandemic on physical health outcomes of patients with schizophrenia spectrum disorders, impact on mental health outcomes, review of case reports and case series to date, treatment recommendation guidelines and risk of increased prevalence of psychosis. CONCLUSIONS: Patients with schizophrenia spectrum disorders may be vulnerable to the effects of the COVID-19 pandemic. This patient population has a number of risk factors, including psychosocial adversities and illness related factors. Continuous monitoring and long-term studies of the impact of the pandemic on this patient population are required.

Incidental finding of age and time disorientation in a clinical sample of patients with schizophrenia: Findings from a short term follow up survey regarding cannabis use.

Age disorientation has been described in a subtype of patients with schizophrenia. The current article reports on an incidental finding from our survey study on patterns of cannabis use pre-post legalization in patients with schizophrenia. For the purpose of the survey study, patients were asked to fill out a total of 41 survey questions. The same participants were contacted over the phone 8 weeks post-legalization. Responses to the survey questions were consistent pre- and post-legalization except for four items which required estimation of time/age. This incidental finding highlights the need for further exploration of this phenomenon by future studies.

What do we know about the pharmacotheraputic management of insomnia in cannabis withdrawal: A systematic review.

BACKGROUND AND OBJECTIVES: Sleep disturbance is one of the hallmarks of cannabis withdrawal. Studies have indicated that treatment of this key symptom may facilitate abstinence. In the present paper we aim to provide a systematic review of the extant literature on pharmacological management of sleep disturbance associated with cannabis withdrawal. METHOD: We conducted a systematic literature search across five electronic databases including PubMed, Psycinfo, MEDLINE, Cochrane review and Embase. Human studies using a pharmacological treatment for sleep disturbances associated with cannabis withdrawal were included. Review articles, case-series, open trials, posters, and editorials were excluded. RESULTS: Seventeen publications, involving 562 participants, were included in this review. Major limitations involved small sample size, high dropout rate, methodological limitations, and heterogeneity of participants. Most of the studies were at high risk of bias, further downgrading the level of evidence. A meta-analysis was not performed due to lack of quantitative data, marked heterogeneity and low quality of the included studies. CONCLUSION: There is not sufficient evidence for any of the reviewed treatment options. Methodological limitations in a majority of the studies rendered their findings preliminary. Of the twelve investigated pharmacological agents, Gabapentin, Lofexidine, Mirtazapine, Quetiapine, and Zolpidem showed some primary benefits for treatment of sleep difficulties associated with cannabis withdrawal; however, future prospective studies are required to confirm such results. SCIENTIFIC SIGNIFICANCE: This review examines the current evidence for potential pharmacological options for treatment of cannabis withdrawal and associated sleep disturbance. It furthers our knowledge and provides groundwork for future research. (Am J Addict 2018;27:453-464).

Self-harm in Child and Adolescent Psychiatric Inpatients: A Retrospective Study.

OBJECTIVE: This study presents a comprehensive report of children and adolescents who engaged in self-harm during their admission to a psychiatric inpatient unit. METHOD: A chart review was conducted on all admissions to an acute care psychiatric inpatient unit in a Canadian children's hospital over a one-year period. Details on patients with self-harm behaviour during the admission were recorded, including: demographics, presentation to hospital, self-harm behaviour and outcome. Baseline variables for patients with and without self-harm behaviour during admission were compared. RESULTS: Self-harm incidents were reported in 60 of 501 (12%) admissions during the one-year period of the study. Fourteen percent of patients (50 of 351) accounted for total number of 136 self-harm incidents. Half of these incidents (49%) occurred outside of the hospital setting, when patients were on passes. Using the Beck Lethality Scale (0-10), mean severity of the self-injury attempts was 0.33, and there were no serious negative outcomes. CONCLUSION: Self-harm behaviour during inpatient psychiatric admission is a common issue among youth, despite safety strategies in place. While self-harm behaviour is one of the most common reasons for admission to psychiatric inpatient unit, our understanding of nature of these acts during the admission and contributing factors are limited. Further research is required to better understand these factors, and to develop strategies to better support these patients.

OBJECTIF: Cette étude présente un rapport détaillé sur les enfants et les adolescents qui se sont adonnés à l'automutilation durant leur séjour dans une unité d'hospitalisation psychiatrique. MÉTHODE: Un examen des dossiers a été mené pour toutes les admissions à une unité d'hospitalisation de soins actifs psychiatriques dans un hôpital pour enfants canadien sur une période d'un an. Les détails sur les patients ayant des comportements d'automutilation durant leur séjour ont été enregistrés, notamment : les données démographiques, la présentation à l'hôpital, le comportement d'automutilation et le résultat. Les variables de départ pour les patients avec et sans comportement d'automutilation durant leur séjour ont été comparées. RÉSULTATS: Des incidents d'automutilation ont été signalés chez 60 sur 501 (12 %) hospitalisations durant la période d'un an de l'étude. Quatorze pour cent des patients (50 sur 351) représentaient le nombre total des 136 incidents d'automutilation. La moitié de ces incidents (49 %) sont survenus à l'extérieur de l'hôpital, quand les patients bénéficiaient d'un laissez-passer. À l'aide de l'échelle de létalité de Beck (0­10), nous avons déterminé que la gravité moyenne des tentatives d'automutilation était de 0,33, et qu'il n'y avait pas de résultats négatifs sérieux. CONCLUSION: Le comportement d'automutilation durant le séjour des patients psychiatriques hospitalisés est un problème commun chez les jeunes, malgré les stratégies de sécurité en place. Bien que le comportement d'automutilation soit l'une des raisons les plus fréquentes de l'hospitalisation dans une unité psychiatrique, notre compréhension de la nature de ces actes durant l'hospitalisation et des facteurs contributifs est limitée. Il faut plus de recherche pour mieux comprendre ces facteurs et pour élaborer des stratégies afin de mieux soutenir ces patients.

Psychological comorbidities and compliance to interventional treatment of patients with cutaneous vascular malformations.

PURPOSE: The aim of this study was to assess qualitatively the psychological stressors affecting patients with cutaneous vascular malformations and hemangiomas (CVM-H) and their impact on compliance to interventional treatment. METHODS: A retrospective chart review was conducted of all patients with CVM-H treated by interventional neuroradiology at a single academic institution during a five-year period (2009-2014). Psychological complaints were documented during each clinic visit by a neuroradiologist. Compliance to interventional treatment was defined by adherence to the scheduled treatment sessions. Fisher's exact test was used to assess for associations between psychological complaints and compliance. RESULTS: Seventy-five patients were assessed, of whom 49 (65.3%) were female, with an age range of 2-78 years (mean age 30.2 years). All except one patient older than seven years of age (n = 71; 94.6%) had a psychological complaint, including fear of negative appearance (n = 53; 70.6%), dissatisfaction with appearance (n = 46; 61.3%), low self-esteem (n = 35; 46.6%), anxiety (n = 16; 21.3%), stress (n = 13; 17.3%), bullying (n = 5; 6.6%), and low mood (n = 4; 5.3%). Twenty-three (31%) patients were non-compliant. Low self-esteem was significantly associated with non-compliance (p = 0.0381). CONCLUSION: There is a high prevalence of psychological comorbidities among patients treated for CVM-H. This has potential implications for interventional treatment, as it was found that low self-esteem is significantly associated with non-compliance. These results suggest the need for early psychological support in these patients in order to maximize compliance to interventional treatment.

Correlates of memory complaints and personality, depression, and anxiety in a memory clinic.

The aim of the study was to find whether there is an association between subjective memory complaint and memory impairment and probable underlying psychological conditions. A total of 90 patients with subjective memory complaint enrolled in this study. Short history and demographic information were obtained and then the patients underwent memory and mental health assessments, using Wechsler Memory Scale (WMS), Hospital Anxiety and Depression Scale (HADS) and Minnesota Multiphasic Personality Inventory (MMPI) test tools. The mean age of the participants was 52.31 ± 17.97. Forty patients out of 90 (44.4%) were male. The prevalence of depression, anxiety and memory impairment was 10%, 12.2%, and 28.8%, respectively. Memory impairment has only shown a significant association with the presence of anxiety disorder according to the HADS findings (P=0.001). Regarding the MMPI, considerable differences were observed in the average grade of hysteria among patients with and without memory impairment: 8.38 ± 2.27 vs. 4.35 ± 1.96. There was also significant statistical association between the average score of depression on the MMPI in patients with and without memory impairment that were 13.7 ± 3.33 and 8.31 ±3.86, (P=0.03). The result of the current study shows that underlying psychological conditions such as anxiety, depression, and histrionic personality are associated with memory impairment.

Use of Electroconvulsive Therapy in Adolescents With Treatment-Resistant Depressive Disorders: A Case Series.

OBJECTIVES: This study presents a comprehensive case series of adolescents who received electroconvulsive therapy (ECT) for treatment-resistant depression. METHODS: Conducting a chart review, we identified 13 adolescents who had ECT for treatment of depression over a 5-year interval (2008-2013) at a Canadian tertiary care psychiatric hospital. Details about participants' clinical profile, index course of ECT, outcome, side effects, and comorbidities were extracted and analyzed. RESULTS: Thirteen adolescents aged 15 to 18 years, received a mean of 14 (SD, 4.5) ECT sessions per patient. Based on the Beck Depression Inventory-II at baseline and after treatment with ECT, a reliable improvement was observed in 10 patients, with 3 achieving full recovery. Through mixed effects linear modeling, we found a decrease of 0.96 points (95% CI, -1.31 to -0.67, P < 0.001) on the Beck Depression Inventory-II total score for every ECT treatment received. The Montreal Cognitive Assessment was used for monitoring of cognitive function throughout the treatment. Adverse effects included transient subjective cognitive impairment (n = 11), headache (n = 10), muscular pain (n = 9), prolonged seizure (n = 3), and nausea and/or vomiting (n = 3). CONCLUSIONS: A clinically significant improvement was observed for 10 (77%) adolescents receiving ECT for treatment-resistant depression. These observations suggest that ECT is a potential treatment option for refractory depression in selected adolescents. More data are needed to draw conclusions about efficacy and possible predictors of treatment response.